SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition

Background Following SARS-CoV-2 infection a significant proportion of convalescent individuals develop the post-COVID condition (PCC) that is characterized by wide spectrum of symptoms encompassing various organs. Even though the underlying pathophysiology of PCC is not known, detection of viral transcripts and antigens in tissues other than lungs raise the possibility that PCC may be a consequence of aberrant immune response to the viral antigens. To test this hypothesis, we evaluated B cell and antibody responses to the SARS-CoV-2 antigens in PCC patients who experienced mild COVID-19 disease during the pre-vaccination period of COVID-19 pandemic. Methods The study subjects included unvaccinated male and female subjects who developed PCC or not (No-PCC) after clearing RT-PCR confirmed mild COVID-19 infection. SARS-CoV-2 D614G and omicron RBD specific B cell subsets in peripheral circulation were assessed by flow cytometry. IgG, IgG3 and IgA antibody titers toward RBD, spike and nucleocapsid antigens in the plasma were evaluated by ELISA. Results The frequency of the B cells specific to D614G-RBD were comparable in convalescent groups with and without PCC in both males and females. Notably, in females with PCC, the anti-D614G RBD specific double negative (IgD-CD27-) B cells showed significant correlation with the number of symptoms at acute of infection. Anti-spike antibody responses were also higher at 3 months post-infection in females who developed PCC, but not in the male PCC group. On the other hand, the male PCC group also showed consistently high anti-RBD IgG responses compared to all other groups. Conclusions The antibody responses to the spike protein, but not the anti-RBD B cell responses diverge between convalescent males and females who develop PCC. Our findings also suggest that sex-related factors may also be involved in the development of PCC via modulating antibody responses to the SARS-CoV-2 antigens

Urinary placental growth factor as a predictor of complications in hypertensive disorders in pregnancy: a protocol for systematic review and meta-analysis

Introduction Preeclampsia is an important cause of maternal and fetal morbidity and mortality. Although the diagnostic and prognostic values of circulating placental growth factor (PlGF) have been extensively studied, urinary PlGF represents an excellent alternative to facilitate sample collection in the follow-up of pregnant women. The aim of this study is to determine whether urinary PlGF levels throughout pregnancy can predict severe maternal, fetal/placental and neonatal complications in women with hypertensive disorders in pregnancy.Methods and analysis Studies that evaluated pregnant women with hypertensive disorders and at least one measurement of urinary PlGF will be included. Studies that measure urinary PlGF after the occurrence of the complications will be excluded. The main outcome will consist of severe maternal complications in women with hypertensive disorders in pregnancy. Secondary outcomes will consist of severe fetal/placental and neonatal complications as defined by the International Collaboration to Harmonize Outcomes for Pre-eclampsia. Prospective cohort studies and case–controls studies reporting original data will be included. Studies will be identified by searching MEDLINE and SCOPUS databases. The first literature search was conducted on 2 March 2020, and another search will be performed before analyses. All eligible studies will be assessed for risk of bias with a standardised 10-items study quality assessment tool adapted from the Study Quality Assessment tools developed by the National Institutes of Health (NIH). Summary of ORs and 95% CIs will be reported to evaluate the association between urinary PlGF levels and hypertensive disorders in pregnancy and its complications. A random-effect meta-analysis will also be performed.Ethics and dissemination Review by an ethics committee will not be required for this systematic review. This study will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and will be submitted for publication in a peer-reviewed journal as well as for presentation at conferences targeting different stakeholders, including researchers, physicians and patients.PROSPERO registration number CRD42020186313

Phenotyping the Responses to Systemic Corticosteroids in the Management of Asthma Attacks (PRISMA): protocol for an observational and translational pilot study

Abstract: Introduction Asthma and its associated exacerbation are heterogeneous. Although severe asthma attacks are systematically prescribed corticosteroids and often antibiotics, little is known about the variability of response to these therapies. Blood eosinophils and fractional exhaled nitric oxide (FeNO) are type 2 inflammation biomarkers that have established mechanistic, prognostic and theragnostic values in chronic asthma, but their utility in acute asthma is unclear. We speculate that the clinical and biological response to those treatments varies according to inflammometry and microbiological test results. Methods and analysis An observational longitudinal pilot study with multimodal clinical and translational assessments will be performed on 50 physician-diagnosed ≥12-year-old asthmatics presenting with an asthma attack and 12 healthy controls, including blood eosinophil count (venous and point-of-care (POC) capillary blood), FeNO and testing for airway infection (sputum cultures and POC nasopharyngeal swabs). People with asthma will be assessed on day 0 and after a 7-day corticosteroid course, with home monitoring performed in between. The primary analysis will be the change in the forced expiratory volume in 1 s according to type 2 inflammatory status (blood eosinophils ≥0.15×109 /L and/or FeNO ≥25 ppb) after treatment. Key secondary analyses will compare changes in symptom scores and the proportion of patients achieving a minimal clinically important difference. Exploratory analyses will assess the relationship between clinical, lung function, inflammatory and microbiome parameters; satisfaction plus reliability indices of POC tests; and sex– gender variability in treatment response. Ultimately, this pilot study will serve to plan a larger trial comparing the clinical and biological response to systemic corticosteroids according to inflammatory biomarkers, offering valuable guidance for more personalised therapeutic strategies in asthma attacks. Ethics and dissemination The protocol has been approved by the Research Ethics Committee of the CIUSSS de l'Estrie–CHUS, Sherbrooke, Quebec, Canada (#2023- 4687). Results will be communicated in an international meeting and submitted to a peer-reviewed journal

Transition to endemic : acceptance of additional COVID-19 vaccine doses among Canadian adults in a national cross-sectional survey

Background Additional doses of COVID-19 vaccine have been proposed as solutions to waning immunity and decreased effectiveness of primary doses against infection with new SARS-CoV-2 variants. However, the effectiveness of additional vaccine doses relies on widespread population acceptance. We aimed to assess the acceptance of additional COVID-19 vaccine doses (third and annual doses) among Canadian adults and determine associated factors. Methods We conducted a national, cross-sectional online survey among Canadian adults from October 14 to November 12, 2021. Weighted multinomial logistic regression analyses were used to identify sociodemographic and health-related factors associated with third and annual dose acceptance and indecision, compared to refusal. We also assessed influences on vaccine decision-making, and preferences for future vaccine delivery. Results Of 6010 respondents, 70% reported they would accept a third dose, while 15.2% were undecided. For annual doses, 64% reported acceptance, while 17.5% were undecided. Factors associated with third dose acceptance and indecision were similar to those associated with annual dose acceptance and indecision. Previous COVID-19 vaccine receipt, no history of COVID-19 disease, intention to receive an influenza vaccine, and increasing age were strongly associated with both acceptance and indecision. Chronic illness was associated with higher odds of acceptance, while self-reported disability was associated with higher odds of being undecided. Higher education attainment and higher income were associated with higher odds of accepting additional doses. Minority first language was associated with being undecided about additional doses, while visible minority identity was associated with being undecided about a third dose and refusing an annual dose. All respondents reported government recommendations were an important influence on their decision-making and identified pharmacy-based delivery and drop-in appointments as desirable. Co-administration of COVID-19 and influenza vaccines was viewed positively by 75.5% of the dose 3 acceptance group, 12.3% of the undecided group, and 8.4% of the refusal group. Conclusions To increase acceptance, targeted interventions among visible minority and minority language populations, and those with a disability, are required. Offering vaccination at pharmacies and through drop-in appointments are important to facilitate uptake, while offering COVID-19/influenza vaccine co-administration may have little benefit among those undecided about additional doses.Medicine, Faculty ofNon UBCPediatrics, Department ofReviewedFacultyResearche

Phenotyping the Responses to Systemic Corticosteroids in the Management of Asthma Attacks (PRISMA): protocol for an observational and translational pilot study

Introduction Asthma and its associated exacerbation are heterogeneous. Although severe asthma attacks are systematically prescribed corticosteroids and often antibiotics, little is known about the variability of response to these therapies. Blood eosinophils and fractional exhaled nitric oxide (FeNO) are type 2 inflammation biomarkers that have established mechanistic, prognostic and theragnostic values in chronic asthma, but their utility in acute asthma is unclear. We speculate that the clinical and biological response to those treatments varies according to inflammometry and microbiological test results.Methods and analysis An observational longitudinal pilot study with multimodal clinical and translational assessments will be performed on 50 physician-diagnosed ≥12-year-old asthmatics presenting with an asthma attack and 12 healthy controls, including blood eosinophil count (venous and point-of-care (POC) capillary blood), FeNO and testing for airway infection (sputum cultures and POC nasopharyngeal swabs). People with asthma will be assessed on day 0 and after a 7-day corticosteroid course, with home monitoring performed in between. The primary analysis will be the change in the forced expiratory volume in 1 s according to type 2 inflammatory status (blood eosinophils ≥0.15×109/L and/or FeNO ≥25 ppb) after treatment. Key secondary analyses will compare changes in symptom scores and the proportion of patients achieving a minimal clinically important difference. Exploratory analyses will assess the relationship between clinical, lung function, inflammatory and microbiome parameters; satisfaction plus reliability indices of POC tests; and sex–gender variability in treatment response. Ultimately, this pilot study will serve to plan a larger trial comparing the clinical and biological response to systemic corticosteroids according to inflammatory biomarkers, offering valuable guidance for more personalised therapeutic strategies in asthma attacks.Ethics and dissemination The protocol has been approved by the Research Ethics Committee of the CIUSSS de l'Estrie–CHUS, Sherbrooke, Quebec, Canada (#2023-4687). Results will be communicated in an international meeting and submitted to a peer-reviewed journal.Trial registration number ClinicalTrials.gov Registry (NCT05870215)

Longitudinal changes in sputum and blood inflammatory mediators during FeNO suppression testing

To explore whether exhaled nitric oxide (FeNO) non-suppression identifies corticosteroid resistance, we analysed inflammatory mediator changes during a FeNO suppression test with monitored high-intensity corticosteroid therapy. In linear mixed-effects models analysed over time, the 15 clinically-distinct ‘suppressors’ (i.e. ≥42% FeNO suppression) normalised asthma control questionnaire scores (mean±SD: 2.8±1.4 to 1.4±0.9, p<0.0001) and sputum eosinophil counts (median [IQR]: 29 [6-41] to 1 [1-5]%, p=0.0003) while significantly decreasing sputum prostaglandin D2 (254 [89-894] to 93 [49-209] pg/mL, p=0.004) and numerically decreasing other type-2 cytokine, chemokine and alarmin levels. In comparison, the 19 non-suppressors had persistent sputum eosinophilia (10 [1-67]% despite high-intensity therapy) with raised end-test inflammatory mediator levels (1.9 [0.9-2.8]-fold greater than suppressors). FeNO non-suppression during monitored treatment implies biological corticosteroid resistance